Patent GB-796839-A (GB)
Title: N,n-disubstituted amides of aryl acetic acids
IPC: C07D333/24
Filed: 1956-06-21
Abstract: The invention comprises N : N-disubstituted arylacetic acid amides of the general formula R.CHR1.COR2 (wherein R is an aryl group, including halo- and alkyl-substituted aryl groups; R1 represents an alkyl, aralkyl, dialkylaminoalkyl, alkoxyalkyl, heterocyclic, alicyclic, heterocyclic alkyl, or arylalkyl carbamoyl methyl group; R2 represents dialkylamino, -N-morpholino-, piperidino-, pyrrolidino-, -N-(alkyl) aralkyl, or -N-(alkyl) aryl) and, when R1 contains an amine substituent, acid addition and quaternary salts thereof; also a process for the preparation of the amides by condensing in substantially equimolar proportions and in the presence of a strongly basic condensing agent an amide of formula RCH2COR2 with a compound R1Y, wherein Y is the residue of a strong acid such as hydrochloric, hydrobromic or p-toluene sulphonic acid; the amides may then be converted to their acid addition salts or quaternary salts with alkyl esters of which the alkyl group contains at most six carbon atoms. Specified condensing agents are sodium amide, phenyl sodium, and sodium hydride, and the reaction is preferably effected in an inert solvent, e.g. benzene, toluene, xylene or dioxan. Suitable salts for therapeutic use include hydrochlorides, maleates, tartrates, citrates, methiodides, ethobromides or dimethyl sulphates. In examples: (1) phenylacetic acid dimethylamide in dry toluene is heated at 80 DEG  C. with sodamide and 3,3-dimethylbutyl chloride to give a -(3,3-dimethylbutyl) phenylacetic acid dimethylamide; similarly (2) to (15), are prepared the following phenylacetic diethylamides: a -(3,3-dimethylbutyl)-, a -(2-ethoxyethyl)-, a -[benzdioxan-(1,4)-methyl-(2)]-, a -(2-thenyl)-, a -(2-morpholinoethyl)-, a -[2-(N-piperidino)-ethyl]-, a -(p-chlorobenzyl)-, a -isoamyl-, a -cyclohexyl-, a -benzyl-, a -(3-diethylaminopropyl)-, and a -pyridyl-; also the dimethyl- and diethylamides of a -(2-pyridyl)-p-chlorophenylacetic acid, the piperidides of a -(2-dimethylaminoethyl)- and a -(3,3-dimethylbutyl)-phenylacetic acid, the N,N-dimethyl amides of a -[2-(N-piperidino) ethyl]-phenylacetic acid, a -[2-(N-piperazino) ethyl]-phenylacetic acid, a [2-(N-piperidino) ethyl]-o-chlorophenylacetic acid, a -benzylphenylacetic acid, a -(2-diethylaminoethyl) phenylacetic acid, and a  - (2 - dimethylaminoethyl) - p - chlorophenylacetic acid, the di-isopropylamides of a -(2-dimethylaminoethyl)-, a -(2-diethylaminoethyl)-, a -cyclohexyl-, and a -(3-diethylaminopropyl)-phenylacetic acid, the morpholides of a -(3-diethylaminopropyl)-, a -benzyl-, a -(2-pyridyl)-, and a -(2-diethylaminoethyl)-phenylacetic acid, the diethylamide of a -(N1,N1-diethylaminoethyl) - a  - (a 1 - naphthyl) acetic acid, the N-n - propyl - N - benzylamides of a  - (2 - dimethylaminoethyl)- and a -(2-diethylaminoethyl) - phenylacetic acid, 2 - phenyl - butandiacid - (1,4) - 1 - (N,N - diethylamide) - 4 - (N1-methyl-anilide), pyrrolidides of a -(2-pyridyl)- and a -(diethylaminoethyl)-phenylacetic acid, N-methylanilides of a -benzyl- and a -(2-diethylaminoethyl)-phenylacetic acid; a -(2-diethylaminoethyl) phenylacetic acid di-n-butylamide, and the corresponding di-isobutylamide; (16) a  - (2 - diethylaminoethyl) - phenylacetic acid di-isopropylamide in ether is treated with methyl iodide to give the quaternary ammonium salt.